Non-spectrophotometric measurement of analyte concentrations and optical properties of objects

ABSTRACT

Improvements in non-invasive detection methods for glucose and other constituents of interest in a sample have been developed. The apparatus and methods of the invention provide an analog of color perception of human vision, preferably in the near infrared region, replacing spectrophotometers and narrow band sources used in other non-invasive near infrared detection methods. A plurality of detector units are used, each covering a broad and overlapping region of the detected spectrum, paralleling color perception and colorimetry. The improvements are primarily concerned with improving the signal-to-background (or noise) ratio such that the data stream is improved. These improvements use congruent sampling, comparison of different data streams from different sample portions or filter sets, using an interrogation system with sufficient speed to allow testing of arterial blood, and using a filter with a spectral structure. In some circumstances, a neural net is used for analysis, allowing the system to learn. A novel method for background discrimination is also described.

REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of U.S. patent applicationSer. No. 914,265, filed Jul. 15, 1992, entitled: "Non-invasive Testing",now U.S. Pat. No. 5,321,265 the disclosure of which is incorporatedherein by reference.

BACKGROUND OF THE INVENTION

The present invention relates to the measurement of the concentration ofconstituents of interest using radiation, preferably near infraredradiation. More particularly, an apparatus has been developed whichutilizes a method of measuring the concentration of constituents such asglucose, alcohol, hemoglobin and its variants such as deoxyhemoglobin,myoglobin, and other reduced or substituted forms of hemoglobin orheme-group containing molecules, drugs of abuse or other clinicalanalytes in a non-invasive manner. Because the apparatus and method donot require a finger puncture to obtain a blood sample, they areparticularly suitable for home glucose testing.

With the spread of AIDS, and the associated fear among the public andhealth care personnel of contracting the disease, development of testingmethods that do not require invasive procedures, including the taking ofblood samples, has become an important goal. Not only AIDS, but otherdiseases such as hepatitis may be spread through invasive procedures ifadequate precautions are not taken. For example, a recent article,"Nosocomiel transmission of Hepatitis B virus associated with the use ofa spring-loaded finger-stick device," New England Journal of Medicine326 (11), 721-725 (1992), disclosed a hepatitis mini-epidemic in ahospital caused by the improper use of an instrument for taking bloodsamples. The article describes how the nurses were unintentionallytransmitting hepatitis from one patient to another with the samplingdevice itself. This type of disease transfer is eliminated bynon-invasive testing.

Effective management of diabetes has also given rise to the need fornon-invasive testing instruments. Many diabetics must measure theirblood glucose levels four or more times a day. Instruments currentlyused for in-home glucose testing require a painful finger prick toobtain a blood sample. Although the price of these instruments hasdropped considerably, such testing requires the use of disposablematerials that can be cumulatively costly. Further, the discomfort,inconvenience, and health risks associated with frequent puncturebleeding are considerable.

Accordingly, a number of groups have recently tried to make non-invasiveinstruments for measuring the concentration of various analytes,particularly blood glucose. Much of the recent development work innon-invasive testing has been exploring the use of the near infraredspectral region (700-1100 nm). This region contains the third overtonesof the glucose spectrum and its use eliminates many of the water bandsand other interference bands that cause potential problems fordetection. However, substantially all of this work has been carried outusing classic spectrophotometric methods. These methods use a set ofnarrow wavelength sources or scanning spectrophotometers which scanwavelength by wavelength across a broad spectrum. The data obtained withthese methods are spectra which require substantial data processing toeliminate (or minimize) the background. Accordingly, the relevant papersare replete with data analysis techniques utilized in an attempt toextract the pertinent information. Examples of this type of testinginclude the work by Clarke, see U.S. Pat. No. 5,054,487, and the work byRosenthal et al., see, e.g., U.S. Pat. No. 5,028,787. Although theClarke work uses reflectance spectra and the Rosenthal work usesprimarily transmission spectra, both rely on obtaining near infraredspectrophotometric data.

One problem with all such methods is that spectrophotometers wereconceived primarily for accurate wavelength-by-wavelength measurement ofspectral intensities. Where, as in non-invasive measurement of theconcentration of glucose and other clinical materials, the analyte ofinterest has weak broadband spectral features and is present in amixture containing other substances with substantially overlappingbroad-band spectral structure, use of classical spectrophotometricmethods employ substantial, and ultimately unsatisfactory, data analysisin an attempt to extract the desired concentration from a background ofinterfering signals. One basic principal of all measurement is, however,that the measurement step determines the information content of thedata, and that computation or transformation adds no information. Inother words, no amount of analysis can make up for the fact that thedistinguishing features of the spectra of the analytes of interest arenot the sharp spectral peaks of classical spectrophotometry but ratherare broad and shallow structures. The analyte is identifiable not by thelocation of its spectral peaks, but by the global structure of itsintensity versus wavelength structure. Since spectrophotometers are notdesigned to generate this kind of information, they are ill-suited formeasurements of this type.

The spectra of the analytes of interest, consisting of a few weak lowresolution features, with overlapping backgrounds, are reminiscent ofthe spectra of reflected, emitted, or transmitted light from coloredobjects in the visible. The human visual system, while an incompetentspectrophotometer, is superb at the subtlest color discrimination andidentification, even under greatly varying illumination conditions.Therefore, the present invention draws on an analogy with thediscrimination of colored objects by the eye, rather than classicspectrophotometric measurements, to obtain data, preferably in theinfrared.

Many related but distinct approaches are possible in developing anapparatus and a method for measuring the concentration of an analyte ofinterest by exploiting the analogy to color perception in the visible.The primary approach is to illuminate the object with broadbandradiation, the analog of white light in the visible, and to use a seriesof spectrally overlapping filters to detect the reflected, emitted ortransmitted radiation to determine the object's relative "color." Thisapproach is disclosed in U.S. patent application Ser. No. 914,265, thedisclosure of which is incorporated herein by reference. The presentapplication concerns modifications and improvement on the method andapparatus described therein to obtain even better data. In fact, many ofthese methods are useful even in classic spectrophotometric systems.

While visual perception is very complex and not completely understood,one approach for relating the concentration of an analyte to absorptionor reflection in the infrared is to obtain and process the raw data asclosely as possible to the known aspects of color perception, utilizinga succession of steps or processing levels. Each step provides a usefulproduct and succeeding steps represent products of greater capability.

The first step to achieve accurate information is the simple analog ofcolor perception using a colorimetry-like approach. Colorimetry isnumerical color communication in which three dimensions are used todescribe the color. It is the trivalent nature of color vision thatpermits color to be specified in a three dimensional space.

There presently are several such three dimensional colorimetry spaces inuse. One of these spaces is the CIE 1931 (x, y)-chromaticity diagram,shown in FIG. 1b, which shows hue and saturation values. Luminosity, thethird dimension, is not shown in FIG. 1b but would be in a Z-direction.FIG. 1a shows the standard observed spectral responses used to generateFIG. 1b.

Another colorimetric space, described in terms of hue, chroma, andvalue, is shown in FIG. 2. This solid can be described as the threenumerical values which can specify any perceived color.

It is important to note that although it is convenient to describe colorin terms of colorimetry, this is not true color perception which is muchmore complex. However, colorimetry is useful for color matching underspecific conditions. An analog of colorimetry, particularly one in theinfrared region, would show similar usefulness in determining analyteconcentration.

There are commercially available colorimeters in the visible formeasuring tristimulus values in terms of luminosity, hue and saturation,yielding numerical values such as are illustrated by FIG. 1. Briefly,these colorimeters use three detectors, with each detector input beingfiltered with a different filter function. Each of the filter functionsand detector responses are chosen to be similar to the three absorptionspectra of the pigments of the three color receptive cones of the humanretina. It appears that no one other than the present inventors havepreviously used, or even considered the use, of an analog of colorperception for wavelength expanded colorimetry for concentrationmeasurements or even applied the method of colorimetry to infraredmeasurements as described herein.

In addition to non-invasive blood measurements for constituents likeglucose, the system could replace present pulse oximeters. Non-invasivemeasurement of arterial oxygen saturation by pulse oximetry is widelyacknowledged to be one of the most important technological advances inclinical patient monitoring. Pulse oximeters measure differences in thevisible and near infrared absorption spectra of fully oxygenated andreduced hemoglobin in arterial blood. Unlike clinical blood gasanalyzers, which require a sample of blood from the patient and can onlyprovide intermittent measurement of patient oxygenation, pulse oximetryprovide continuous, and instantaneous, measurement of blood oxygenlevels.

However, current commercial oximeters, and their algorithms areinaccurate under conditions of low pulse pressure and/or low oxygensaturation. These severe conditions are observed in the normal unbornfetus or where the features of interest are broad. Unlike thetransmission sampling of the commercial oximeters, space limitationsassociated with the fetus require that the spectral data be obtained byreflectance sampling. It has been suggested that a new analysistechnique using multivariate calibration methods can improve theprecision, accuracy and reliability of quantitative spectral analysis.Even these techniques are limited by the type of input data.

The apparatus and methods of U.S. patent application Ser. No. 914,265solves this problem by providing infrared analogs of colorimetry. Whilethe data provided is better than that from spectrophotometers,signal-to-background can always be improved, thereby providing evengreater sensitivity.

Accordingly, an object of the invention is to provide an apparatus whichprovides an improved measure of the concentration of a constituent ofinterest or a determination of optical properties of an object in asample using an analog of color perception.

Another object of the invention is to provide an improved method ofaccurately, inexpensively, and quickly measuring the concentration ofclinical analytes in a non-invasive manner using an analog ofcolorimetric analysis.

A further object of the invention is to provide an improved apparatusfor, and a method of, non-invasive concentration measurements using theanalogs of colorimetry and color perception that allows for convenientsample insertion and removal and is not responsive to radiation fromextraneous sources.

A still further object of the invention is to provide an apparatus forand a method of determinations of the concentration of an analyte ofinterest, or a determination of the optical properties of an object,with an improved signal-to-background level.

These and other objects and features will be apparent from thedescription and the accompanying drawings.

SUMMARY OF THE INVENTION

The present invention features an improved apparatus and methods forcarrying out testing for concentration of constituents of interest ordetermining the optical properties of an object, preferably in anon-invasive manner. U.S. patent application Ser. No. 914,265 disclosesan apparatus which uses, and expands upon, an analog of human vision todevelop data through non-invasive testing which is much improved fromthat available through classic spectrophotometric measurements. In itsvarious embodiments, the present invention discloses improvements on thebasic concept and apparatus described in the aforementioned U.S. patentapplication Ser. No. 914,265; in particular, the present inventionconcerning ways of improving the signal-to-background (or noise) ratiosuch that the data stream is improved. As such, these improvements areimportant as they allow better standardization and use of the basicinvention in circumstances where the more simplified apparatus might notprovide meaningful data.

The basic apparatus such has been described in the aforementioned patentapplication, which is useful for non-invasive testing of theconcentration of a constituent or analyte of interest, e.g., in amammalian blood stream, has

(1) a light source generating illuminating radiation, preferablyinfrared radiation, for illuminating a portion of mammalian tissue,

(2) a sample chamber for fixing the portion of the mammalian tissue in asubstantially fixed location relative to the light source,

(3) detection means having a plurality, that is, at least 2, preferablyat least 3 or 4, detectors, each of the detectors having a separate peakspectral response and an overlap in overall spectral response with atleast one other detector. While the detector itself can provide theaforementioned spectral response, preferably the detector has in concerta filter which transmits a portion of the spectrum of illuminatingradiation emitted by the light source. Each of these filters has aseparate peak transmission response and broad enough transmissionresponse such that there is partial overlap in transmissioncharacteristics with at least one other of the filters. The apparatusalso includes analysis means for analyzing the outputs from thedetectors to generate a signal indicative of the concentration of theconstituent or analyte or the optical properties of an object.

In one aspect of the invention, the improvement is in the form ofarranging (and manufacturing) the apparatus such that "congruentsampling" is achieved. In congruent sampling, each detector receives theradiation from substantially the same portion of the sample transmitted(or reflected or emitted) in the same direction so that all the raysemerging in all directions from each point of the sample are incident inthe same direction on each detector. With congruent sampling, thedetectors are superimposable; that is, if a transformation (ortranslocation) was made from the position of one detector to theposition of another detector the identical optical sampling is achieved.Congruent sampling guarantees that the optical beam path from the sampleto each detector is both of equal length and of equal angles, therebyeliminating a substantial portion of error caused by viewing fromunequal distances or angles. This aspect of the invention isparticularly relevant in dealing with inhomogeneous samples, since itminimizes errors due to the inhomogeneity. Further, the use of congruentsampling allows a larger source and a larger illumination area, thusallowing the delivery of the same cumulative power to the detectorwithout using a very small spot. For measurements of a body part, thisminimizes discomfort and allows greater source selection flexibility.Congruent sampling, as well as some of the other improvements describedherein, also assist in correcting for modifications in response due totemperature or changes in refractive index. These effects may arise inthe instrument or the sample itself.

Preferably, in this and all of the other aspects of the invention,infrared radiation in the 700-2500 nm range is used as the illuminatingradiation, although wavelengths as low as 500 nm or up to about 10,000nm may provide meaningful information and are not ruled out. If threedetectors are used, the analysis means generates an output which is (orcan be) an infrared analog of a location in a colorimetric threedimensional space; if more detectors are used, an output is generatedwhich is an analog of an n-dimensional colorimetric space, where n isequal to, or less than, the number of detectors. One of the detectorsthat is often used in addition to the plurality of detectors is ablack/white luminosity detector which is responsive to and overlaps thespectral response of all of the other detectors. This black/whiteluminosity detector is used to show the presence and absence of signalsas a whole without regard to the specific wavelength. The analysis meanscan be a computer but preferably is a neural network which mimics thehuman mind. Neural networks are becoming more sophisticated and the useof this type of network provides a "teaming curve" to the system as awhole. If the system is used for concentration testing, a sample chamberis normally required. The sample chamber can hold a mammalian body partsuch as fingers, ears, hands, foot, toe, wrist, tongue or even theforehead in fixed relation to the detectors. Basically, all that isneeded for a non-invasive test measurement using this system issufficient vascular tissue such that the blood vessel bed can be sampledto sufficient depth in either transmittance or reflectance mode so as toprovide meaningful data.

The apparatus (and methods) are particularly useful in detecting theconcentration of a broad family of analytes and constituents found inmammalian blood streams. Obvious choices for applicability of theinvention include glucose, glucose indicating constituents (it may bepossible to read a constituent that gives an indication of glucose levelinstead of glucose itself), cholesterol, lipids, hemoglobin and itsvariants, drugs of abuse and/or drugs of abuse indicating constituents.These drugs of abuse include not just narcotics and hallucinogens butalso materials such as alcohol. Any analyte with absorption bands in theresponse range of the detectors can be used. Further, the apparatus canbe used to measure water bands as well as the constituent of interest,thereby facilitating the determination of concentration. The constituentmay shift the water bands toward its color which can provide theindicating activity even if the bands of the constituent itself areindistinct; that is, the fractional shift of the water bands may presentthe sought for information.

In another aspect, the invention features having at least two detectionmeans or sets of detectors, each of said detection means either viewinga different portion of the sample, e.g., mammalian body or having adifferent set of filters from the other. Using either of these apparatusvariations, one obtains two distinct sets of signals which can becorrelated to concentration or the optical properties of the object. Bycorrelating these two signal sets, one can obtain bettersignal-to-background values, since the alignment (or correlation) of thesignals does not necessarily provide alignment of background, therebysmoothing the background and providing better-signal-to-backgroundratios. A preferred method of achieving this is to have differentdetection means for each of two fingers, possibly with different sets offilters for each, thereby getting two different sets of data that,however, are correlated to the same analyte concentration. If a singlesample is used, the detectors, or most preferably the filters for eachof the detection means, should have differing spectral transmissionresponses. The analysis means obtains an output from a first detectionmeans which is an analog of a location in a colorimetric n-dimensionalspace, it obtains an output from the second detection means which is ananalog of a location in an m-dimensional space, and compares the twooutputs to provide a measure of the constituent of interest. Both m andn are equal to or less than the number of detectors in the respectivedetection means. If two distinct body parts are used, either with orwithout different filter sets on the separate detection means, thereshould be at least two sample chambers. Each of said sample chambersmust be arranged such that the radiation passing through falls on onlyone, but not both, of the first and second detection means.

In still another aspect of the invention, at least one of the filtersfor the detectors in the detection means can be replaced by a filterwhich either has a spectral structure, such as a comb filter, or by anarrow pass filter, which has all of its transmission range overlappedby one of the other filters. A filter having spectral structure such asa comb filter is equivalent to a series of filters, yielding anapproximation of more detectors. A sinusoidal filter is a preferred typeof comb filter but a sine squared or other filter having spectralstructure could be used. The advantage of using this type of filteringunit is that absorption bands for unwanted analytes can be eliminatedeven if they are in the active area by paralleling the absorptioncharacteristics of the comb filter with those absorption bands, orselecting narrow band filters such that the absorption characteristicsof the analytes do not overlap with the transmission characteristics ofthose filters.

In still a further aspect of the invention, an interrogation unit ormeans is included in the apparatus which interrogates the outputs fromthe detectors in a sufficiently rapid manner so as to allowdifferentiation of constituents of interest in arterial blood, asopposed to venous or tissue blood. This interrogation means can be thecombination of the detection means and the analysis means so long as theelectronics provides processing or collection of data which issufficiently rapid so that the time of the arterial pulse is longcompared with the interrogation time. Since the amount of blood in boththe veins and tissues is substantially constant, this allows anapproximation of the transmission or reflection from tissues and veinsas a constant, thereby assisting in differentiating the arterial signalfrom background. The analysis means can use absolute values fortransmission or reflection, or preferably, one can calculate a ratebased on the slope of the arterial pulse signals.

In addition to the multiple variations on the apparatus, there also arecorresponding method variations which form various aspects of theinvention. For example, the congruent sampling or equal optical beampath/equal angle apparatus forms a method of minimizing the effect ofsample inhomogeniety not only with respect to variability over theobserved sample surface but also variability in sample transmission as afunction of angle. This ensures that each detector in each detectionmeans (or channel) sees only the same view of the same portion of thesample and that the detectors therefore process only color differencessince the geometric and inhomogeniety effects are identical in allchannels. The other methods provide similar advantages. Preferably, somecombination of the apparatus described previously can be used; forexample, two different body parts may be used with separate detectorunits and the processing should be sufficiently fast that an arterialpulse is seen by each of the detection filter units. This againminimizes the background level. An FTIR instrument could also be used topractice the methods of the invention if its orthogonal Fourier filtersare replaced by a filter set such as is previously described anddirecting the outputs of these new filter functions to a unit whichperforms this described processing. Further, the invention can bepracticed with a fluorescent object or sample if the filters ordetectors are selected for the fluorescent radiation emitted by thesample rather than the illuminating radiation.

Other aspects and features of the invention will be more readilyapparent from the following description and the drawing.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows the CIE 1931 chromaticity plot, shown in standard spectraltristimulus values (FIG. 1a) and normalized form (FIG. 1b);

FIG. 2 is a three dimensional plot of color in terms of hue, chroma andvalue;

FIGS. 3a-b show computer models of water and sugar peaks plotted asabsorbance versus wavelength; and

FIG. 3c shows the composite transmission spectrum of a glucose solution;

FIGS. 4a and 4b are plots of relative spectral response versuswavelength for two different filter sets, one having four differentfilters and the other with six different filters;

FIGS. 5a and b are two parallel embodiments of the invention showing amethod of providing detectors which all view the same portion of thesample at the same optical beam path through the same solid angle, withFIG. 5b having a sufficient number of detectors to parallel the twodetector means embodiment of FIG. 8;

FIG. 6 is a schematic illustration of the device using a fiber opticbundle to provide equal distance and equal angle to the detectors;

FIG. 7 is a detail of the fiber optic cable at a line 1--1 from FIG. 6;

FIG. 8 shows an embodiment of the invention having two sample chambersand two detection means;

FIG. 9 shows the transmittance of a "comb" filter useful in anotherembodiment of the invention;

FIGS. 10(a)-(d) shows pulse data taken from an instrument using theprinciples of another embodiment of the invention; and

FIG. 11 is rate data using the same data and apparatus as is used inFIG. 10.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides improved non-invasive procedures formeasuring the concentration of a constituent of interest that hasabsorbance, emittance, or reflectance bands in a selected region of theelectromagnetic spectrum, preferably 500-10,000 nm, most preferably700-2500 nm. This invention can be used to determine optical propertiesof a sample or object in addition to making concentration measurements.The apparatus and methods are improvements to the basic conceptdescribed in U.S. patent application Ser. No. 914,265. The apparatus andmethods of the prior application are based, in part, on the recognitionthat present problems associated with non-invasive concentrationmeasurements that use radiation as a probe relate to the type ofinformation that is obtained, e.g., from spectrophotometers, rather thanthe processing of the information itself.

Although using different analysis techniques can clarify whatinformation has been obtained, these analysis techniques cannot generateresults better than the underlying information obtained. By applying ananalog of color perception to concentration measurements, particularlyforming a near infrared parallel of the three different pigments of thecones of the retina, significantly better information relating toconcentration can be obtained. Since in color perception "colorconstancy" is maintained under extreme variations in illumination, theuse of neural networks or digital computation to process information ina manner more similar to the information processing of the eye-brain ispreferred. Color constancy is the capacity to successfully recover thereflected, emitted, or transmitted color of an object regardless of thecomposition or intensity of the ambient illuminating radiation. Afurther description of color constancy is found in Dufort and Lumsden,"Color categorization and color constancy in a neural network model ofV4", Biol. Cybern. 65, 293-303(1991), the disclosure of which isincorporated herein by reference.

The improvements herein to the basic invention set forth in U.S. patentapplication Ser. No. 914,265 concern improved means of obtaining datasuch that the signal desired is maximized and the background signal (ornoise) is minimized. Each of the embodiments described herein providealternate means to achieve this same advantage. In fact, a preferredapparatus could have a combination of several of these embodiments usedin concert.

FIGS. 1 and 2 show different ways of handling data in classicinstrumental colorimetry. FIG. 1a shows the CIE 1931 standard colormatching functions, which approximate the spectral response of the threetypes of cones in the human retina. FIG. 1b, a so-called chromaticityplot, is a convenient two dimensional representation of the systematicvariation of this standard observer to monochromatic light of differentwavelengths. Each point on the continuous curve in FIG. 1b is plotted asa normalized (X, Y) pair, where the values are obtained from the threeresponse curves in FIG. 1a by dividing by the sum of all three response,according to the formulas:

D=x'+y'+z' X=x'/D Y=y'/D Z=z'/D

This normalization lead to the result X+Y+Z=1 and completely defines therelative values of X, Y, and Z. Accordingly, specification of X and Y onthe two dimensional plot in FIG. 1b is sufficient to specify Z as well.Monochromatic light passes at the indicated points along the horseshoeshaped curve in FIG. 1b and with this normalization, pure monochromaticlight falls at the same point along the curve irrespective of itsintensity or brightness so the intensity (nominally D) must be specifiedseparately. White light (of any intensity) fails at the point X=0.307Y=0.314 (the point designated WL on FIG. 1b).

The light received from real objects, which is not monochromatic, fallat points within the interior of the curve. The hue or dominant "color"of such real objects is defined as the perceived color of themonochromatic light which lies at the intersection of the outerhorseshoe-shaped curve with a line from the white light point (WL)through the object's location on the plot. Line WL-R is an example ofthis type of line and point R shows the "hue". The saturation, orchroma, of the light is a measure of how far along the line from "white"to "pure" color the object's location is found.

The hue-chroma coordinate system in FIG. 1b is irregular, however, inthat the length of the vector from the center to the outer curve changessignificantly with wavelength. FIG. 2 is an alternative, cylindricalcoordinate system in which the hue is defined by the angular rotationfrom an arbitrarily chosen green-red axis, and the chroma is defined asthe radial distance from the center. Here the density, or value of thelight is explicitly included as the third cylindrical coordinate. The ABplane in FIG. 2 is equivalent to the XY plane in FIG. 1b.

In classic instrumental colorimetry, only the color was sought, so thatthe relative direction of the vector in the three dimensional space waswhat was important, not the amplitude. When used for color comparison,the tristimulus system outlined in conjunction with FIG. 1 reduces thedimensionality of the vector space from three to two through the use ofnormalization. It should be noted, however, that this self-normalizedapproach introduces a degree of linearization for incremental colorchanges which alter the three components of the xyz vector by relativelysmall amounts, particularly when the changes are nearly perpendicular tothe starting vector itself.

These instrumental tristimulus systems do not, however, perform colorvision, but rather are intended to characterize colors so they can beduplicated reliably. In particular, these systems are quite sensitive tochanges in the illuminant spectrum and, hence, are not duplicating thecolor constancy features of mammalian color vision.

The present invention sets up an analog of visual color perception usingN detectors which can form a partially degenerate N-dimensional vectorspace. The dimensionality is preferably reduced by at least one becausethe vector is normalized, and perhaps by more than one because thedetector curves overlap strongly so that the resultant detector signalsare partially correlated. Many different normalizations, such as the sumof one or more of the N signals or the length of the vector, may beused. The resultant vector space is used to characterize a higherdimensional analog of hue and chroma to quantify the amount of the"color" of glucose in the observed specimen.

FIG. 3 is a series of computer-generated simulations of the absorbancespectrum of water and sugar in the 700-1200 nm range. The locations,magnitudes, and widths of the peaks shown are taken from a variety ofsources in the literature. The three indicated peaks near 1000, 920, and840 nm appear together, for example, in the work of Koashi et al.described in U.S. Pat. No. 4,883,953, superimposed on a broad backgroundoffset. Interpretation of such reported results requires care toseparate glucose spectral features from instrumental artifacts. Thedifficulty in obtaining reliable glucose spectra is well-known, andfollows from the small magnitude of the absorption by glucose in thisspectral range and from the fact that the water content and refractiveindex of solutions change when glucose is added. The instrumentallyobserved changes in detector signals in this spectral range are amixture of increased absorbance from glucose, decreased absorbance dueto the displaced water and changes in instrumental throughput due torefractive index and temperature variations during the experiments. Thefinal result for the glucose spectrum itself is highly dependent on theaccuracy of the corrections for these effects. Nevertheless, the generalfeatures shown in FIG. 3 emerge as suitably descriptive to guide theselection of detector response functions to implement the presentinvention.

The peak (WOH) shown in FIG. 3a at 960 nm is attributed to absorption bythe OH group in water. The glucose peak (GOH) near 1000 nm in FIG. 3b isalso attributed to OH absorption, with its location shifted to higherwavelength as a result of local field distortions at the OH sites on theglucose due to the other atoms on the molecule. The size of the glucosepeak can be readily estimated on the assumption that there is no loss oftotal absorbance, but only a shift. Thus, pure water is roughly 56molar; glucose at 1 gram/dl (=10 grams/liter) and a molecular weight of180 is roughly 10/180=0.056 molar, 1000 times smaller than pure water.Each molecule of glucose, however, carries 5 OH groups: hence theglucose is roughly 0.28 molar in OH groups, and should have anabsorbance about 200 times smaller than pure water. Scaling from FIG.3a, the expected magnitude of the shifted OH peak from glucose is thusof the order of 0.001 absorbance units.

The peaks shown in FIG. 3b near 920 nm (CCH) is attributed to thestretch mode of the CH bonds in glucose. Its magnitude relative to theshifted OH peak (GOH) in FIG. 3b is taken coarsely from the datapresented by Koashi, as is the smaller peak at 840 nm. These three peaksare consistent with the spectral correlation plots presented byRosenthal in U.S. Pat. No. 5,028,787, which also indicate the possiblepresence of another slight peak in the 750 nm range, which has not beenincluded in FIG. 3b.

FIG. 3b also includes an estimate of the relative size of the absorbanceof the water displaced by glucose at 1 gram/dl concentration. This wasobtained from FIG. 3a using the tabulated specific gravity of 1.0039(ref. Handbook of Chemistry and Physics) for such a glucose solution.Thus, if 1 gram of glucose is added to 99 grams of water, the result is100 grams of solution filling 100/1.0039=99.61 ml. A full deciliter ofthis solution then contains 99.39 grams of water (and 1.0039 grams ofglucose). By comparison a full deciliter of pure water would contain 100grams of water. Thus the change to approximately 1 gram/dl concentrationof glucose reduces the water content of the solution by 0.61 grams; themagnitude of the absorbance of this displaced water is about 100/0.61 orabout 164 times smaller than that of pure water.

FIG. 3c shows the calculated impact of these broad and shall glucosefeatures on the transmission spectrum of four centimeters of water. Notethat the glucose concentration has been increased to 10 grams/dl torender the difference between the curves visible. The major impact ofthe glucose absorbance is to change the apparent shape of the 960 nmwater band (WOH). The total change is slight: at the clinicallysignificant range of 0.05-0.5 grams/dl, the changes would fall withinthe width of the line on the full scale plot in FIG. 3c.

The need to detect and quantify such small changes in the presence ofother changes in the band shape due to temperature effects and theimpact of other constituents of the fluid which may also alter the shapeplace a premium on making optimal use of the entire signal change due toglucose, i.e., by integrating the full change with different weights ona plurality of overlapping detectors. The information in FIG. 3 may makeit possible to "tune" the filters to emphasize the CH stretch andshifted OH band contribution, and diminish that from the unshifted OHband contribution, in one or more detectors, while doing the reverse inother detectors.

FIG. 4a shows one set of filters which could be used with the invention.Each of the four response curves is a composite of the spectral responseof the silicon detector (HAMMATSU S2387 Series) and the transmission ofat least one 3 mm thick Schott glass filter. If a pair of filters isused (as in filter sets A, B and C), the filters are in series. In eachof case A, B and C, the first illuminated filter in the pair is along-pass filter whose transmission rises with increasing wavelength(RG9, RG780, RG850, respectively). The second filter, made of KG2 glass,acts as a short-pass filter whose transmission falls with increasingwavelength. For the D detector, a single filter such as a RG1000 filteris used and the decrease in response at the highest wavelengths isproduced by the spectral response of the silicon detector itself.

As can be seen from this figure, each of the filters has a separate peaktransmittance range, and overlaps with the response of the others. Inparticular, the A, C, and D filters comprise a trio which implements anapproximate translation of the cone response curves from the visibleinto the near infrared, as described in U.S. patent application Ser. No.914,265.

However, the filter set in FIG. 4a is not an efficient match to thespectra of glucose and water, because a large portion of the response isconcentrated in the short wavelength region where these constituents areleast absorbing. FIG. 4b shows an alternative set of filters which couldincrease the percentage impact of the various bands in FIG. 3 on thetotal signal in each detector. This shows overlapping broad-bandinterference filters which are commercially available from the CorionCorporation (their P70 series) to bracket the 960 nm water peak so as toenhance the size and uniqueness of the signal changes which result fromchanging glucose concentration.

It is also possible to create filters with multiple passbands so that,for example, the H and J filters in FIG. 4b could be combined into asingle composite passband. Similarly, a comb or sinusoidal filter, asshown in FIG. 9, could be used to integrate the signal from all three ofthe glucose peaks in FIG. 3, with a similar but spectrally displacedfilter being used to de-emphasize the spectral regions which contain theglucose features. The width, shape, and amplitude of each lobe of thecomb, and the number of lobes in each set, can be adjusted to optimizethe separation of signal and background. To achieve the desiredself-consistent normalization of the signals, each detector signal couldbe divided, for example, (i) by the vector length calculated from all ofthe signals together, (ii) by the simple sum of all of the signals,(iii) by the signal observed through a single broadband filter whichoverlapped most of the spectral range covered by the full set, or even(iv) by the signal observed in a narrow band filter placed at anappropriate location within the range. Such normalization techniques andrelated ones are well known in the art of data processing, and are notrestricted to the one delineated above; the important quality is thatthe filter response curves overlap, and be matched in width and locationto the broad and shallow spectral features of the analyte of interest.

FIGS. 5 and 6 both show attempts to cure one of the problems associatedwith any type of radiation measurement, the inhomogeneity derived fromphysical differences in the view of the detectors relative to thesample. With any physical object, particularly something asinhomogenious as mammalian body part, if the optical beam paths from thesample to the detector, and the solid angles over which they operate,are not equal, the device itself may cause an unwanted error (or atleast a reduced signal-to-background response). The basic concept of thedevices illustrated by these Figures is that the detectors collect lightleaving points at the entrance aperture congruently. "Congruent," asused herein, means that the light collection efficiency at each point inthe extended object being viewed, relative to the other points in theobject, is the same for each detector. In other words, the images foreach detector should be fully superimposable, so that, they cover theexact same solid angle at the same distance. The device illustrated inFIG. 5 achieves this by using a series of beam splitters to make theoptical beam path such that the detectors all receive the same signal atthe same distance and same angle. The device of FIG. 5 has a lamp 10which generates the illuminating radiation, preferably infraredradiation in the 700-2500 nm range. The light from this lamp 10 isfocused by a launch lens 20 through an aperture 30. Aperture 30 leads toa sample chamber 40, which is shown having a portion of the finger 45therein. Radiation transmitted through finger 45 goes through entranceaperture 52 in detection means 50. Because the size of transmittedsignals is lower, reflectance measurements may be advantageous butreflectance can have other associated problems with stray radiation.Further, although a mammalian body part is preferred, any sample couldbe used. Detection means 50 has a series of beam splitters 60, 62 and 64which split the light entering through entrance aperture 52 and send itto four detectors 72, 74, 76 and 78. Each of detectors 72, 74, 76 and 78may have an associated filter 82, 84, 86 and 88, respectively. Thesedetectors and their associated filters, which will be described in moredetail below, all have different peak transmittance responses. Normally,they also have sufficiently broad transmittance response such that eachdetector has some overlapping spectrum of transmittance with at leastone other detector.

The outputs from detectors 72, 74, 76 and 78 go to an analysis means,such as a computer or neural network (not shown), which provides dataprocessing and generates a signal indicative of the concentration of theconstituent of interest.

FIG. 5b shows a parallel device but with eight rather than fourdetectors and associated filters. This system could provide moreaccurate information by using more detectors and can be used in lieu ofthe two sample chamber/eight detector device shown in FIG. 8. Forcertain samples, segregating the data into two sets, each of fourdetectors, improved data can be obtained compared to a single detectorset.

FIG. 6 illustrates another variation of the apparatus that providessubstantially equal optical beam paths over the same solid angle. Inthis embodiment, lamp 10' and launch lens 20' can be identical to lamp10 and 20 in embodiment of FIG. 5. In place of the entrance aperture tothe sample chamber 30, a fiber optic cable 30' is used. Fiber opticcable 30' can either be a single fiber optic line or could be a fiberoptic bundle such as is described later in conjunction with FIG. 7.Fiber optic cable 30' delivers the illuminating radiation, preferablyinfrared radiation in the 700-2500 nm range, to finger 45' is located.Although a finger is used in each of the Figures as a mammalian bodypart, other body parts including the forehead, toes, hands, feet, earsor wrist could be used, or a different type of sample could be used.

At the exit of sample chamber 40', the light transmitted through a fiberoptic bundle 52' which takes the place of entrance aperture 52. Thelight is transmitted to detection means 50 through a fiber optic cable52' which is bifurcated into four optic cables, 62', 64', 66' and 68'.The bifurcated fiber optic cable take the place of beam splitters 60, 62and 64. Each of these fiber optic cables 62', 64', 66' and 68', lead tofilters 82', 84', 86', and 88' which then transmit radiation todetectors 72', 74', 76' and 78'. The detectors and filters can beidentical to those shown in FIG. 5.

The critical aspect of the device shown in FIG. 6 is the exit fiberoptic cable bundle 52'. FIG. 7 shows a detail of this fiber optic cablebundle. FIG. 7 is a cross section of fiber optic bundle 52' through theline 1--1 prime on FIG. 6. As can be seen, this fiber optic bundle 52'contains many small fibers from the four output legs, 62', 64', 66',68', intertwined so that they effectively sample each point at the inputsubstantially equally. As shown in the Figure, all of the fibers havingthe number 1 go to bifurcated fiber optic cable 62', those having thenumber 2 go to fiber optic cable 64', those having the number 3 go tofiber optic cable 66', and those having the number 4 go to fiber opticcable 68'. While this is not exactly equivalent to the beam splitterarrangement FIG. 5 since the fibers do not exactly overlay each other,it is a very good first order of approximation if there are sufficientfibers, and the fibers are sufficiently small such that the mix offibers about the cable is substantially random and equal.

FIG. 8 illustrates another embodiment of the invention, one whereby twodistinct n-dimensional spaces (or an n-dimensional space and anm-dimensional space) are generated and compared to yield an improvedsignal. In the embodiment shown, lamp 10" is used to provide theilluminating radiation which then goes to two mirrors 15" and 16" andonto a pair of launch lens 20". Each of entrance apertures 30", samplechambers 40", exit aperture 52" and detector means 50" are identical,both to that shown in FIG. 5 and to each other. However, in onesub-embodiment, the filters 82", 84", 86", and 88" in the two detectionmeans 50" are different, yielding different n (or m) dimensional spaces.If these filters are different in that they have different peaktransmittance, a different n (e.g., 3) dimensional space is generated.Each detector means generates a signal indicative of the concentrationof the material of interest such as glucose and the two values can becompared by the analysis means to eliminate some of the contribution ofbackground. One means of doing this is to generate a vector such aspreviously described, align the vectors, and add them which should givea higher vector amplitude in a single direction. Since the backgroundcomponents should not align, this yields better separation of signal andbackground. In the illustrated embodiment, two separate sample chambers40" are shown. These sample chambers could be used for different bodyparts, such as two fingers, and a value generated even if the filtersets 82", 84", 86" and 88" are identical. Since the glucose values inthe blood should be the same but the background values between thefingers are likely be different, this will promote differentiation ofsignal-from-background. In another aspect of this embodiment of theinvention, a single sample chamber could be used but a beam splitter isplaced near the exit aperture 52" from the sample chamber 40" such thatthe exiting transmitted radiation (or reflected radiation if that formatis used) goes to two parallel detection means 50". By using differentfilter sets 82", 84", 86" and 88" on these two detection means 50" withthe same input signal to the filters, two different n-dimensional (or ann-dimensional and m-dimensional) spaces are generated and the sameadvantages as previously described are obtained.

FIG. 9 shows the transmittance of a comb filter which could be used asone of the filters in a detection means in various aspects of theinvention. This filter has a spectral structure such that it absorbs atcertain wavelengths and transmits at other wavelengths. By aligning theabsorbance bands of the filter with known bands of backgroundconstituents which are to be eliminated, e.g., water bands, one canobtain a more highly differentiated data stream. In place of the combfilter or other filter having a spectral structure, a single filter (ormultiple filters) having a single, narrow transmittance peak which isoverlapping with at least one of the other filters, could be used.

FIG. 10 shows actual arterial pulse data with an early form of theinstrument described herein. The electronics of the instrument are suchthat one can collect data over a hundred times per second, much fasterthan the pulse rate. Accordingly, individual pulses can be shown on anabsorbance versus time graph. In FIG. 10, each of sub FIGS. 10A-10D showsignal output voltages in volts versus time in milliseconds. Each of thefour FIGS. 10A-10D, are made using the same type of photocells, siliconphotocells, with different filter sets, specifically those with theresponse shown in FIG. 4a. Similarly, different photocells such as amixture of silicon, lead sulfide and lead selenide cells could be used.The classic notch in the pulse wave form is seen in the figure. What isinteresting is that the four different filters not only transmitdifferent mounts of light (based on the transmittance of light ofparticular frequency), but also that the ratios of peak to troughvoltages are different for each different detector. Using this type ofinformation, a value of concentration can be obtained for theconstituent of interest.

FIG. 11 uses the same data as FIG. 10 but plots it as a normalized raterather than an absolute voltage value. The Y axis shows a percent changeper second by plotting average slope across a unit time divided by theaverage value across a sliding sampling window in time, while the X axisgives time in milliseconds. The actual rate is inverted here but as isseen from FIGS. 11A-11D, the rate is different in each detector. Sincethese type of rate calculations have been used previously in pulseoximetry to provide information (albeit at limited wavelengths withoutoverlap as the present case), a parallel can be made between the presentinvention and the rate calculations of pulse oximetry which areparticularly useful. In fact, this type of arterial pulse processing canbe used with any of the embodiments of the invention and it isparticularly useful in conjunction with the dual sample chamber (e.g.,two finger) method because the arterial components in each finger willcorrelate strongly. Similarly, it is believed that transmittance andreflectance changes from the arterial pulse will improve results usingthe present methods and apparatus. By using only the arterial pulse,much of the background can be eliminated and more meaningful data may begenerated.

Those skilled in the art may appreciate the other advantages and uses ofthe subject matter disclosed herein. Such other advantages, uses andembodiments of the apparatus and methods described herein are includedin the following claims.

What is claimed is:
 1. In an apparatus for determining the concentrationof a constituent of interest in a sample having:a radiation sourcegenerating a spectrum of illuminating radiation for illuminating aportion of said sample; a sample chamber for fixing said portion of saidsample in a substantially fixed location relative to said radiationsource; detection means having a plurality of detectors adapted togenerate an output responsive to radiation transmitted by emitted by orreflected from, said sample, each of said detectors having a spectralresponse in a portion of said spectrum of illuminating radiation emittedby said radiation source, each of said detectors having a separate peakspectral response and at least a partial overlap in spectral responsecharacteristics with that of at least one other of said detectors; andanalysis means tier analyzing said outputs from the detectors togenerate a signal indicative of the concentration of said constituent;the improvement comprising: said apparatus being constructed such thateach of said detectors is located such that it congruently samples theradiation from said sample.
 2. The apparatus of claim 1 wherein saidilluminating radiation comprises infrared radiation in the 700-2500 nmrange.
 3. The apparatus of claim 1 wherein said analysis means generatesan output which is an analog of a location in a colorimetricn-dimensional space, n being equal to, or less than, the number ofdetectors in said detection means.
 4. The apparatus of claim 1 whereinsaid detector means further comprises a black/white luminosity detectorwhich is responsive to and overlaps said spectral response of all ofsaid plurality of detectors.
 5. The apparatus of claim 1 wherein each ofsaid detectors comprises a filter which transmits or reflects a portionof said spectrum of illuminating radiation, each of said filters havinga separate peak transmittance or absorbance response different from thepeak transmittance or reflectance responses of the other filters of saiddetection means and at least a partial overlap in transmittance orreflectance response with at least one other of said filters.
 6. Theapparatus of claim 1 wherein said analysis means comprises a neuralnetwork.
 7. The apparatus of claim 1 wherein at least one of saidplurality of detectors comprises a silicon photocell.
 8. The apparatusof claim 1 wherein said sample comprises a portion of a human body. 9.The apparatus of claim 1 wherein said constituent of interest isselected from the group consisting of glucose, glucose indicatingconstituents, cholesterol, lipids, proteins, hemoglobin and itsvariants, drugs of abuse and drugs of abuse indicating constituents. 10.The apparatus of claim 1 comprising beam splitting means to allow saidplurality of detectors to be arranged to achieve congruent sampling. 11.The apparatus of claim 1 comprising a fiber optic cable bundlescontaining a plurality of optical fibers to allow said plurality ofdetectors to be arranged to achieve congruent sampling.
 12. In anapparatus for determining the concentration of a constituent of interestin a sample having:a radiation source generating a spectrum ofilluminating radiation for illuminating a portion of said sample; asample chamber for fixing said portion of said sample in a substantiallyfixed location relative to said radiation source; detection means havinga plurality of detectors adapted to generate an output responsive toradiation transmitted by emitted by, or reflected from said sample, eachof said detectors having a spectral response in a portion of saidspectrum of illuminating radiation emitted by said radiation source,each of said detectors having a separate peak spectral response and atleast a partial overlap in spectral response characteristics with thatof at least one other of said detectors; and analysis means foranalyzing the outputs from said detectors to generate a data signalindicative of the concentration of said constituent; the improvementcomprising: having at least two detection means, a first detection meansgenerating a first data stream formed of a composite of a data signalcomponent indicative of said concentration of said constituent and abackground component and a second detection means generating a seconddata stream formed of a composite of a data signal component indicativeof said concentration of said constituent and a background component;and said analysis means comprising means adapted for comparing saidfirst data stream with said second data stream in order to generate aninformation signal indicative of the concentration of said constituentwhile rendering the interfering features of the background from saidfirst and second data streams to be less distinct than the background isin either data stream individually.
 13. The apparatus of claim 12wherein each of said detectors comprises a filter which transmits orreflects a portion of said spectrum of illuminating radiation, each ofsaid filters having a peak transmittance or reflectance responsedifferent from the peak transmittance or reflectance responses of theother filters of said detection means and at least a partial overlap intransmittance or absorbance response with at least one other filter,said first detection means having a first set of filters and said seconddetection means having a second set of filters, and said first andsecond sets of filters having differing transmittance or reflectanceresponses.
 14. The apparatus of claim 12 wherein said illuminatingradiation comprises infrared radiation in the 700-2500 nm range.
 15. Theapparatus of claim 12 wherein said analysis means generates an analog ofa location in a colorimetric n-dimensional space from said first datastream, where n is equal to or less than, the number of detectors ineach of said first detection means; an analog of a location in acolorimetric m-dimensional space from said second data stream, where mis equal to or less than, the number of detectors in said seconddetection means; and compares said locations to generate said datasignal indicative of concentration.
 16. The apparatus of claim 12wherein at least one of said detection means further comprises ablack/white luminosity detector which is responsive to and overlaps saidspectral response of all of said plurality of detectors in saiddetection means.
 17. The apparatus of claim 12 wherein said analysismeans comprises a neural network.
 18. The apparatus of claim 12 whereinat least one of said plurality of detectors comprises a siliconphotocell.
 19. The apparatus of claim 12 wherein said sample comprises aportion of a human body.
 20. The apparatus of claim 12 wherein saidconstituent of interest is selected from the group consisting ofglucose, glucose indicating constituents, cholesterol, lipids, proteins,hemoglobin and its variants, drugs of abuse and drugs of abuseindicating constituents.
 21. The apparatus of claim 12 wherein saidapparatus comprises at least two sample chambers, each of said samplechambers being arranged such that radiation passing there through fallson only one, but not both, of said first and second detection means. 22.In an apparatus for determining the concentration of a constituent ofinterest in a sample having:a radiation source generating a spectrum ofilluminating radiation for illuminating a portion of said sample; atleast one sample chamber for fixing said portion of said sample in asubstantially fixed location relative to said radiation source;detection means having a plurality of detectors adapted to generate anoutput, each of said detectors having a spectral response to a portionof said spectrum of illuminating radiation emitted by said radiationsource, each of said detector having a separate peak spectral responseand at least a partial overlap in spectral response characteristics withthat of a least one other of said detectors; and analysis means foranalyzing the outputs from said detectors to generate a data signalcomponent component indicative of the concentration of said constituent;the improvement comprising: having at least two detection means, a firstdetection means adapted to receive radiation transmitted or reflectedfrom a first sample portion which is in a first sample chamber, saidfirst detector means generating a first data stream formed of acomposite of a data signal component indicative of said concentration ofsaid constituent and a background component, and a second detectionmeans adapted to receive radiation transmitted or reflected from asecond sample portion which is in a second sample chamber, said seconddetection means generating a second data stream formed of a composite ofa data signal component indicative of said concentration of saidconstituent and a background component; and said analysis meanscomprising means adapted for comparing said first data stream with saidsecond data stream in order to generate an information signal indicativeof the concentration of said constituent while rendering the interferingfeatures of the background from said first data stream and said seconddata stream to be less distinct than the background is in either datastream individually.
 23. The apparatus of claim 22 wherein each of saiddetectors has a filter with a peak spectral response different from thepeak spectral responses of the other filters of said detection means andat least a partial overlap in spectral response with at least one otherfilter, said first detection means having a first set of filters andsaid second detection means having a second set of filters, and saidfirst and second sets of filters having differing spectral transmittanceor reflectance responses.
 24. The apparatus of claim 22 wherein saidilluminating radiation comprises infrared radiation in the 700-2500 nmrange.
 25. The apparatus of claim 22 wherein said analysis meansgenerates an analog of a location in a colorimetric n-dimensional spacefrom said first data stream, where n is equal to or less than, thenumber of detectors in each of said first detection means; an analog ofa location in a colorimetric m-dimensional space from said second datastream, where m is equal to or less than, the number of detectors insaid second detection means; and compares said locations to generatesaid data signal component indicative of concentration.
 26. Theapparatus of claim 22 wherein at least one of said detection meansfurther comprises a black/white luminosity detector which is responsiveto and overlaps said spectral response of all of said plurality ofdetectors in said detection means.
 27. The apparatus of claim 22 whereinsaid analysis means comprises a neural network.
 28. The apparatus ofclaim 22 wherein at least one of said plurality of detectors comprises asilicon photocell.
 29. The apparatus of claim 22 wherein said samplecomprises a portion of a human body.
 30. The apparatus of claim 22wherein said constituent of interest is selected from the groupconsisting of glucose, glucose indicating constituents, cholesterol,lipids, proteins, hemoglobin and its variants, drugs of abuse and drugsof abuse indicating constituents.
 31. In an apparatus for determiningthe concentration of a constituent in a sample having:a radiation sourcegenerating a spectrum of illuminating radiation for illuminating aportion of said sample; a sample chamber for fixing said portion of saidsample in a substantially fixed location relative to said radiationsource; detection means having a plurality of detectors adapted togenerate an output, each of said detectors having a filter whichtransmits or reflects a portion of the spectrum of illuminatingradiation emitted by said radiation source, each of said filters havinga separate peak transmittance or reflection response and at least apartial overlap in transmittance or reflectance characteristics with atleast one other of said filters; and analysis means for analyzing theoutputs from the detectors to generate a signal indicative of theconcentration of said constituent; the improvement comprising: having atleast one of said filters in said detection means being selected fromthe group consisting of filters having spectral structure such that ithas multiple absorbance bands in the portion of the spectrum over whichit transmits or reflects radiation, and filters which have only a singlenarrow transmittance or reflectance range.
 32. The apparatus of claim 31wherein said illuminating radiation comprises infrared radiation in the700-2500 nm range.
 33. The apparatus of claim 31 wherein said analysismeans generates an output which is an analog of a location in acolorimetric n-dimensional space, n being equal to, or less than, thenumber of detectors in said detection means.
 34. The apparatus of claim31 wherein said detector means further comprises a black/whiteluminosity detector which is responsive to and overlaps said spectralresponse of all of said plurality of detectors.
 35. The apparatus ofclaim 31 wherein said analysis means comprises a neural network.
 36. Theapparatus of claim 31 wherein at least one of said plurality ofdetectors comprises a silicon photocell.
 37. The apparatus of claim 31wherein said sample comprises a portion of a human body.
 38. Theapparatus of claim 31 wherein said constituent of interest is selectedfrom the group consisting of glucose, glucose indicating constituents,cholesterol, lipids, proteins, hemoglobin and its variants, drugs ofabuse and drugs of abuse indicating constituents.
 39. The apparatus ofclaim 31 wherein said spectral structure of said filter is in the formof a sinusoidal transmittance or reflectance structure.
 40. In anapparatus for determining the concentration of a constituent in a samplehaving:a radiation source generating a spectrum of illuminatingradiation for illuminating a portion of said sample; a sample chamberfor fixing said portion of said sample in a substantially fixed locationrelative to said radiation source; detection means having a plurality ofdetectors adapted to generate an output, each of said detectors having aspectral response in a portion of the spectrum of illuminating radiationemitted by said radiation source, each of said detectors having aseparate peak spectral response and at least a partial overlap inspectral response characteristics with at least one other of saiddetectors; and analysis means for analyzing the outputs from thedetectors to generate a data signal component indicative of theconcentration of said constituent; the improvement comprising: providinginterrogation means which collects the outputs from said detectors insufficiently rapid manner to observe a distinct arterial pulse wave formso to allow differentiation of constituents of interest in arterialblood, as opposed to venous or tissue blood, in said sample.
 41. Theapparatus of claim 40 wherein each of said detectors comprises a filterwhich transmits or reflects a portion of said spectrum of illuminatingradiation, each of said filters having a separate peak transmittance orabsorbance response different from the peak transmittance or reflectanceresponses of the other filters of said detection means and at least apartial overlap in transmittance or reflectance response with at leastone other of said filters.
 42. The apparatus of claim 40 wherein saidilluminating radiation comprises infrared radiation in the 700-2500range.
 43. The apparatus of claim 40 wherein said analysis meansgenerates an output which is an analog of a location in a colorimetricn-dimensional space, where n is equal to, or less than, the number ofdetectors in said detection means.
 44. The apparatus of claim 40 whereinsaid detection means further comprises a black/white luminosity detectorwhich is responsive to and overlaps said spectral response of all ofsaid plurality of detectors.
 45. The apparatus of claim 40 wherein saidanalysis means comprises a neural network.
 46. The apparatus of claim 40wherein each of said plurality of detectors comprise silicon photocells.47. The apparatus of claim 40 wherein said sample comprises a portion ofa human body.
 48. The apparatus of claim 40 wherein said constituent ofinterest is selected from the group consisting of glucose, glucoseindicating constituents, cholesterol, lipids, proteins, hemoglobin andits variants, drugs of abuse and drugs of abuse indicating constituents.49. The apparatus of claim 40 whereby said apparatus comprises aplurality of sample chambers, each sample chamber being adapted to holda separate portion of mammalian tissue.
 50. The apparatus of claim 49wherein each of said sample chambers has a detection means associatedtherewith, each of said individual detection means having its own set offilters associated therewith.
 51. A method for determining theconcentration of a constituent of interest in a sample comprising thesteps of:fixing a portion of said sample of interest in a position suchthat it can be illuminated with a spectrum of radiation from a radiationsource; illuminating said portion of said sample of interest with saidspectrum of radiation from said radiation source; detecting radiationtransmitted or reflected from said sample, said detection being carriedout by detection means containing a plurality of individual detectors,each of said detectors having a peak spectral response distinct from thepeak spectral response any other of said detectors, said detectors eachhaving overlap in spectral response with at least one of said otherdetectors, each of said detectors being located relative to said fixedportion of said sample such that each of said detectors providescongruent sampling with the others of said detectors; generating a datastream corresponding to said detected radiation from each of saiddetectors; and analyzing said data streams to obtain a measure ofconcentration.
 52. The method of claim 51 wherein each of said detectorsfurther comprise an associated filter, each of said associated filtershaving a peak transmittance or reflectance distinct from the peaktransmittance or reflectance of any of the other of said filters, eachof said filters having an overlap in spectral response with at least oneother of said filters.
 53. The method of claim 51 wherein said spectrumof illuminating radiation comprises infrared radiation in the 700-2500nm range.
 54. The method of claim 51 wherein said analysis stepcomprises forming an analog of a specific position in an n-dimensionalcolorimetric space from said data stream, n being equal to, or lessthan, the number of detectors in said detection means.
 55. The method ofclaim 51 wherein said analysis step is carried out by a neural network.56. The method of claim 51 wherein said neural network is calibrated andtrained to process said data streams to achieve an analog of colorconstancy in vision.
 57. The method of claim 51 wherein said constituentof interest is selected from the group consisting of glucose, glucoseindicating constituents, cholesterol, lipids, proteins, hemoglobin andits variants, drugs of abuse, and drugs of abuse indicatingconstituents.
 58. The method of claim 51 wherein said sample comprises aportion of a human body.
 59. The method of claim 51 comprising beamsplitting means to allow said plurality of detectors to be arranged toachieve congruent sampling.
 60. The method of claim 51 comprising afiber optic cable bundles containing a plurality of optical fibers toallow said plurality of detectors to be arranged to achieve congruentsampling.
 61. A method for determining the concentration of aconstituent of interest in a sample comprising the steps of:fixing aportion of said sample of interest in a position such that it can beilluminated with a spectrum of radiation from a radiation source;illuminating said portion of said sample of interest with said spectrumof radiation from said radiation source; detecting radiation transmittedor reflected from said sample, said detection being carried out by atleast a first detection means and a second detection means eachcontaining a plurality of individual detectors, each of said detectorshaving a peak spectral response distinct from the peak spectral responseany other of said detectors in the same detection means, said detectorshaving an overlap in spectral response with at least one of said otherdetectors in said same detection means, whereby said first detectionmeans generates a first data stream formed of a composite of a datasignal component indicative of said concentration of said constituentand a background component and said second detection means generates asecond data stream formed of a composite of a data signal componentindicative of said concentration of said constituent and a backgroundcomponent; and said analysis means compares said first data stream withsaid second data stream in order to generate an information signalindicative of the concentration of said constituent while rendering theinterfering features of the background from said first and second datastreams to be less distinct than the background in either data streamindividually.
 62. The method of claim 61 wherein each of said detectorsfurther comprise an associated filter, each of said associated filtershaving a peak transmittance or reflectance distinct from the peaktransmittance or reflectance of any other of the said filters, each ofsaid filters having an overlap in spectral response with at least oneother of said filters.
 63. The method of claim 61 wherein said spectrumof illuminating radiation comprises infrared radiation in the 700-2500nm range.
 64. The method of claim 61 wherein said analysis stepcomprises forming at least two distinct analogs of specific positions indistinct colorimetric spaces from said signals, an n-dimensional spacefrom said first detection means where n is equal to, or less than, thenumber of detectors in said first detection means, and an m-dimensionalspace from said second detection means, where m is equal to, or lessthan, the number of detectors in said second detection means, andcorrelating said analog positions for said first and second detectionmeans.
 65. The method of claim 61 wherein said analysis step is carriedout by a neural network.
 66. The method of claim 65 wherein said neuralnetwork is calibrated and trained to process said signals to achieve ananalog of color constancy in human vision.
 67. The method of claim 61wherein said constituent of interest is selected from the groupconsisting of glucose, glucose indicating constituents, cholesterol,lipids, proteins, hemoglobin and its variants, drugs of abuse, and drugsof abuse indicating constituents.
 68. The method of claim 61 whereinsaid sample comprises a portion of a human body.
 69. A method fordetermining the concentration of a constituent of interest in a samplecomprising the steps of:fixing a portion of said sample of interest in aposition such that it can be illuminated with a spectrum of radiationfrom a radiation source; illuminating said portion of said sample ofinterest with a spectrum of radiation from said radiation source;detecting radiation transmitted or reflected from said sample, saiddetection being carded out by detection means containing a plurality ofindividual detectors, each of said detectors having an associated filterwhich has a peak transmittance or reflectance distinct from the peaktransmittance or reflectance any other of said filters, said filterseach having overlap in transmittance or reflectance characteristics withat least one of said other filters, at least one of said filters beingselected from the group consisting of filters having a spectral responsesuch that it has reflectance or transmittance bands in the portion ofthe spectrum over which it transmits or reflects radiation, and filterswhich have only a narrow transmittance or reflectance range; generatinga signal corresponding to said detected radiation from each of saiddetectors; and analyzing said signals to obtain a measure ofconcentration.
 70. The method of claim 69 wherein said illuminatingradiation comprises infrared radiation in the 700-2500 nm range.
 71. Themethod of claim 69 wherein said analysis step comprises forming ananalog of a specific position in an n-dimensional colorimetric spacefrom said signals, where n is equal to, or less than, the number ofdetectors in said detection means.
 72. The method of claim 69 saidanalysis step is carded out by a neural network.
 73. The method of claim72 wherein said neural network is calibrated and trained to process saidsignals to achieve an analog of color constancy in vision.
 74. Themethod of claim 69 wherein said constituent of interest is selected fromthe group consisting of glucose, glucose indicating constituents,cholesterol, lipids, proteins, hemoglobin and its variants, drugs ofabuse, and drugs of abuse indicating constituents.
 75. The method ofclaim 69 wherein said sample comprise a portion of a human body.
 76. Amethod for determining the concentration of a constituent of interest ina sample comprising the steps of:fixing a portion of said sample ofinterest in a position such that it can be illuminated with a spectrumof radiation from a radiation source; illuminating said portion of saidsample of interest with a spectrum of radiation from a radiation source;detecting radiation transmitted or reflected from said sample, saiddetection being carried out by detection means containing a plurality ofindividual detectors, each of said detectors having a peak spectralresponse distinct from the peak spectral response of any other of saiddetectors, said detectors each having overlap in spectral responsecharacteristics with at least one of said other detectors; collectingoutputs from each of said detectors using a interrogation means whichhas a sufficiently rapid response to observe a distinct arterial pulsesuch that the data collected can be correlated to arterial blood levelsof said constituent of interest; generating a data signal componentcorresponding to said collected outputs; and analyzing said data signalcomponent components to obtain a measure of concentration.
 77. Themethod of claim 76 wherein each of said detectors further comprise anassociated filter, each of said associated filters having a peaktransmittance or reflectance distinct from the peak transmittance orreflectance of any other of the said filters, each of said filtershaving an overlap in transmittance or reflectance characteristics withat least one other of said filters.
 78. The method of claim 76 whereinsaid illuminating radiation comprises infrared radiation in the 700-2500nm range.
 79. The method of claim 76 wherein said analysis stepcomprises forming an analog of a specific position in an n-dimensionalcolorimetric space from said signals, where n is equal to, or less than,the number of detectors in said detection means.
 80. The method of claim76 wherein said analysis step is carried out by a neural network. 81.The method of claim 80 wherein said neural network is calibrated andtrained to process said signals to achieve an analog of color constancyin vision.
 82. The method of claim 76 wherein said constituent ofinterest is selected from the group consisting of glucose, glucoseindicating constituents, cholesterol, lipids, proteins, hemoglobin andits variants, drugs of abuse, and drugs of abuse indicatingconstituents.
 83. The method of claim 76 wherein said sample comprises aportion of a human body.
 84. The method of claim 76 wherein saiddetection means comprises a plurality of detection means, each of saiddetection means having filters associated therewith to generate adistinct signal from any other of said detection means, and wherein saidanalysis of said signals comprises comparing said signals obtained fromeach of said detector means.